Project Summary Sex differences play a critical role in regulating diverse behaviors in human and nonhuman species. In humans, several neuropathologies such as Alzheimer's and schizophrenia exhibit gender biases suggesting the existence of gender-specific neural connectivity patterns. Therefore, it is essential to elucidate neural processing pathways that each gender utilizes in response to diverse cues. The overarching goal of our research is to understand olfactory coding of social cues in different sexes at the molecular, cellular and circuit levels. This proposal aims to decipher the neural network involved in processing of cues specific for a single gender. We will address how sensory information is organized at multiple levels within the brain to encode sex-specific instinctive behaviors. Olfactory information from the environment is detected by multiple sensory structures like the main olfactory epithelium (MOE) and vomeronasal organ (VNO). These structures transduce this information to the second-order and third order neurons creating an olfactory space of the environment in the brain. However, little is known about how information from the olfactory organs builds internal maps of olfactory space in the higher cortex generating learned or innate behavioral responses. Here we propose a circuit-based approach to understand how sex-specific circuits transduce and organize olfactory sensory information to mediate instinctive behaviors. We are proposing using a novel combinatorial approach involving neurophysiology, optogenetics and behavioral genetics to understand information processing in a gender-specific olfactory circuit. Aim-1 will focus on characterizing the functional connections within the male-specific sensory neurons, to understand the encoding of concentration preferences of the different cues. Aim-2 will understand how the patterns of activity in sensory neurons relate to the activation of these specific downstream interneurons. Aim-3 will address the mechanisms of neuromodulation within the male-specific sensory circuit. By elucidating the functional connectome of a gender- specific sensory circuit, we will reveal fundamental solutions into olfactory processing in gender- specific connectivity maps of vertebrates thereby providing a better understanding of many neurological and psychiatric diseases, particularly those showing strong sex biases such as schizophrenia and Alzheimer's disease.